The purpose of this project is to compare the antitumor effects of 3 known stimulants of macrophages (BCG, C. parvum, glucan) in 3 tumor models (Walker 256 in rats, L1210 in DBA/2 mice and sarcoma 180 in mice) in order to more precisely determine, with respect to nonspecific macrophage activity, (a) how each stimulant acts (similarities and differences) to induce tumor resistance, (b) which agent is the most effective, and (c) by what protocol to produce maximum antitumor effects. The production of activated macrophages capable of inducing tumor remission produces humoral (mediators) and macrophage cellular (metabolic) changes. By examining basic similarities and differences in the possible sites and intensity of action of BCG, C. parvum and glucan against strain and nonstrain-specific tumor models in 2 different species (rats and mice), we will be able to better understand the essential response(s) elicited by each of the 3 stimulants and the tumor models selected for study. The aspecific opsonin (also called HRF), which does play an apparent role in neoplasia, and MIF will be followed as well as selected macrophage metabolic activities (O2 uptake, protein synthesis, glucose oxidation, enzyme activities) in order to assess what role humoral and metabolic changes play in the remission of these tumors by this nonspecific means. We will, separately, manipulate the levels of the aspecific opsonin (HRF) (with gelatin or the lipid emulsion), and cellular metabolic activities (with trypan blue, hydrocortisone, methyl palmitate) of macrophages in in vivo and in vitro studies to help determine sites of action of each agent. Thus, we will determine, on a comparative basis, how, by what means, and to what degree each stimulant can act to induce increased resistance with each tumor model. This has obvious clinical significance.